CN111526895A

CN111526895A - Disinfection system and method using nitric acid vapor

Info

Publication number: CN111526895A
Application number: CN201880084563.XA
Authority: CN
Inventors: 卡尔布·T·尼尔森; 德鲁·M·威廉森; 阿萨姆谱塔·A·G·本纳阿尔斯-艾登
Original assignee: 3M Innovative Properties Co
Current assignee: 3M Innovative Properties Co
Priority date: 2017-12-29
Filing date: 2018-12-26
Publication date: 2020-08-11
Also published as: EP3731877A2; WO2019130220A2; US20210093739A1; WO2019130220A3

Abstract

A decontamination system includes an enclosure and a source of decontamination vapor coupled to the enclosure, wherein the decontamination vapor includes nitric acid. Also described is a method of sterilizing a contaminated article, the method comprising placing the contaminated article within an enclosure of a sterilization system, and treating the contaminated article within the enclosure with a source of sterilization vapor comprising nitric acid for a treatment time sufficient to sterilize the contaminated article by achieving a reduction in the number of colony forming units of the sterilized contaminated article relative to the contaminated article. Subjecting the soiled article within the enclosure to the source of sanitizing steam may comprise alternately subjecting the soiled article to sanitizing steam for a first time interval and subjecting the soiled article to water steam for a second time interval.

Description

Disinfection system and method using nitric acid vapor

Technical Field

The present disclosure relates generally to sterilization or disinfection of medical equipment and articles, and more particularly to the application of nitric acid vapor to effect sterilization or disinfection of medical articles, such as medical instruments or endoscope lumens.

Background

Reliable supply of sterile equipment, instruments and supplies is of vital importance to modern medical practice. Various types of equipment are known for sterilizing or disinfecting reusable items in a hospital environment, including for example steam autoclaves. U.S. Pat. No. 4,301,113(Alguire et al); us patent 4,294,804 (Baran); U.S. patent 5,317,896(Sheth et al); U.S. patent 5,399,314(Samuel et al); us patent 3,571,563 (Shulz); us patent 3,054,270 (Huston); and U.S. patent 3,564,861(Andersen et al) discusses sterilization equipment and its control system.

Items that cannot withstand autoclaving temperatures can be sterilized with a sterilizer using a biocidal gas such as ethylene oxide. Although ethylene oxide, nitrogen dioxide and other gaseous nitrogen oxides have been used as disinfectants or sterilants, these gases also exhibit undesirable toxicity and, in the case of ethylene oxide, flammability. For at least these reasons, the art has sought alternative forms of disinfectants or sterilants.

Disclosure of Invention

The present disclosure provides a disinfection or sterilization system and a disinfection or sterilization method that employ a disinfection vapor containing nitric acid vapor as a disinfectant or sterilant.

Accordingly, in one aspect, the present disclosure describes a decontamination system including an enclosure and a source of decontamination vapor connected to the enclosure, wherein the decontamination vapor includes nitric acid. Optionally, the closed chamber is connected to a vacuum pump.

In another aspect, the present disclosure describes a method of sterilizing a contaminated article comprising placing the contaminated article within an enclosure of a sterilization system, and treating the contaminated article within the enclosure with a source of sterilization vapor comprising nitric acid for a treatment time sufficient to sterilize the contaminated article by achieving a reduction in the number of colony forming units of the sterilized contaminated article relative to the contaminated article. Optionally, the closed chamber is connected to a vacuum pump.

Additional exemplary embodiments within the scope of the present disclosure are provided in the following list of exemplary embodiments.

List of exemplary embodiments

A. A decontamination system comprising an enclosed chamber and a source of decontamination vapor connected to the enclosed chamber, wherein the decontamination vapor comprises nitric acid, optionally wherein the enclosed chamber is connected to a vacuum pump.

B. The sterilizing system of embodiment a wherein the sterilizing vapor further comprises a gas selected from the group consisting of molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof.

C. The sanitization system of embodiment B, wherein the sanitization steam comprises air.

D. The sterilization system according to any of the preceding embodiments, further comprising a source of water vapor in a gas connected to the enclosed chamber, wherein the gas is selected from molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof. Optionally wherein the relative humidity of the water vapour in the gas is at least 20%.

E. The sterilization system according to any one of the preceding embodiments, further comprising a device for removing at least a portion of the nitric acid from the sterilization vapor, optionally wherein the device comprises a material selected from the group consisting of: a basic functional compound, a reducing agent, a basic absorbent, a basic adsorbent, a catalyst, activated carbon, a molecular sieve, or a combination thereof.

F. The sterilization system according to any of the preceding embodiments, further comprising a contaminated article undergoing sterilization, optionally wherein the contaminated article is contaminated with at least one of: a biofilm consisting of a plurality of microorganisms, a biofilm consisting of a plurality of microbial spores, a biofilm consisting of a plurality of fungal spores, or a plurality of fungal spores.

G. The sterilization system of embodiment F, wherein the contaminated article is a medical article, optionally wherein the medical article is selected from a medical dressing, a medical device, or a combination thereof.

H. The sterilization system of embodiment G wherein the medical device is an endoscope having a hollow lumen, further wherein the sterilization vapor passes through the hollow lumen of the endoscope.

I. The sterilization system according to any one of embodiments F through H, wherein the biofilm comprises a plurality of microorganisms selected from the group consisting of: bacillus stearothermophilus (Geobacillus stearothermophilus), Bacillus subtilis (Bacillus subtilis), Bacillus atrophaeus (Bacillus atrophaeus), Bacillus megaterium (Bacillus megaterium), Bacillus coagulans (Bacillus coagulogenes), Clostridium producing (Clostridium sporogenes), Bacillus pumilus (Bacillus pumilus), Aspergillus brasiliensis (Aspergillus brasiliensis), Aspergillus oryzae (Aspergillus oryzae) Aspergillus oryzae (Aspergillus oryzae), Aspergillus niger (Aspergillus niger), Aspergillus nidulans (Aspergillus nidulans), Aspergillus flavus (Bacillus difficile), Clostridium difficile (Clostridium difficile), Mycobacterium tuberculosis (Mycobacterium tuberculosis), Staphylococcus aureus (Escherichia coli), Staphylococcus aureus (Staphylococcus epidermidis), Staphylococcus aureus (Staphylococcus aureus), Escherichia coli (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus aureus), Escherichia coli (Bacillus subtilis), Bacillus subtilis (Bacillus subtilis), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus aureus), Bacillus subtilis), and Bacillus subtilis), Bacillus, Propionibacterium acnes (Propionibacterium acnes), Klebsiella pneumoniae (Klebsiella pneumoniae), Enterobacter cloacae (Enterobactercloacae), Proteus mirabilis (Proteus mirabilis), Salmonella enterica (Salmonella enterica), Salmonella typhi (Salmonella typhi), Shigella flexiriri (Shigella flexirii), and combinations thereof.

J. A method of sterilizing a contaminated article, the method comprising placing the contaminated article within an enclosed chamber of a sterilization system, optionally wherein the enclosed chamber is connected to a vacuum pump; and subjecting the contaminated article within the enclosure to a source of sterilizing steam comprising nitric acid for a treatment time sufficient to sterilize the contaminated article by achieving a reduction in the number of colony forming units of the sterilized contaminated article relative to the contaminated article, optionally wherein the treatment time is at most ten minutes.

K. The method of embodiment J, wherein the sterilizing vapor further comprises a gas selected from molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof.

L. the method of embodiment K, wherein the sterilizing vapor comprises air.

M. the method of any one of embodiments J, K or L, wherein treating the soiled article within the enclosed chamber with the sterilizing steam source comprises alternately subjecting the soiled article to sterilizing steam for a first time interval and subjecting the soiled article to steam for a second time interval, optionally wherein alternately subjecting the soiled article to sterilizing steam for the first time interval and subjecting the soiled article to steam for the second time interval is performed at least twice.

The method of any one of embodiments J, K, L or M, further comprising removing nitric acid from the disinfection vapor using a material selected from the group consisting of: a basic functional compound, a reducing agent, a basic absorbent, a basic adsorbent, a catalyst, activated carbon, a molecular sieve, or a combination thereof.

The method of any one of embodiments J, K, L, M or N, wherein the contaminated article is contaminated with at least one of: a biofilm comprising a plurality of microorganisms, a biofilm comprising a plurality of microbial spores, a biofilm comprising a plurality of fungal spores, or a plurality of fungal spores.

P. the method of any one of embodiments J, K, L, M, N or O, wherein the contaminated article is a medical article, optionally wherein the medical article is selected from a medical dressing, a medical device, or a combination thereof.

Q. the method of embodiment P, wherein the medical device is an endoscope having a hollow lumen, further wherein the sterilizing steam is passed through the hollow lumen of the endoscope.

R. the method of any one of embodiments O, P or Q, wherein the contaminated article is contaminated with a biofilm comprising a plurality of microorganisms selected from the group consisting of: bacillus stearothermophilus (Geobacillus stearothermophilus), Bacillus subtilis (Bacillus subtilis), Bacillus atrophaeus (Bacillus atrophaeus), Bacillus megaterium (Bacillus megaterium), Bacillus coagulans (Bacillus coagulogenes), Clostridium producing (Clostridium sporogenes), Bacillus pumilus (Bacillus pumilus), Aspergillus brasiliensis (Aspergillus brasiliensis), Aspergillus oryzae (Aspergillus oryzae), Aspergillus niger (Aspergillus niger), Aspergillus nidulans (Aspergillus nidulans), Aspergillus flavus (Aspergillus flavus), Clostridium difficile (Clostridium difficile), Mycobacterium tuberculosis (Mycobacterium tuberculosis), Mycobacterium tuberculosis (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus epidermidis), Staphylococcus aureus (Staphylococcus aureus), Escherichia coli (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Bacillus subtilis), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis), Bacillus, Propionibacterium acnes (Propionibacterium acnes), Klebsiella pneumoniae(ii) bacteria (Klebsiella pneumoniae), Enterobacter cloacae (Enterobacter cloacae), Proteus mirabilis (Proteus mirabilis), Salmonella enterica (Salmonella enterica), Salmonella typhi (Salmonella typhi), Shigella (Shigella flexirii), and combinations thereof, further wherein the treatment time is at least 1 minute and the reduction in colony forming units of the sterilized article relative to the contaminated article is at least 2-log₁₀And at most 11-log₁₀Optionally wherein the treatment time is at most six minutes.

S. the method of any of embodiments O, P, Q or R, wherein the contaminated article is contaminated with a plurality of microorganisms, further wherein the treatment time is at least 1 minute and the reduction in the number of colony forming units of the sterilized article relative to the contaminated article is at least 4-log₁₀And at most 9-log₁₀Optionally wherein the treatment time is up to six minutes.

T. the method of any one of embodiments O, P, Q, R or S, wherein the contaminated article is contaminated with a plurality of microbial spores or a plurality of fungal spores, wherein the treatment time is at least 1 minute and the reduction in the number of colony forming units of the sterilized article relative to the contaminated article is at least 6-log₁₀And at most 10-log₁₀Optionally wherein the treatment time is up to six minutes.

Various aspects and advantages of exemplary embodiments of the present disclosure have been summarized. The above summary is not intended to describe each illustrated embodiment or every implementation of the present certain exemplary embodiments of the present disclosure. The following drawings and detailed description more particularly exemplify certain preferred embodiments using the principles disclosed herein.

Drawings

The disclosure may be more completely understood in consideration of the following detailed description of various embodiments of the disclosure in connection with the accompanying drawings, in which:

fig. 1 is a schematic view of an exemplary disinfection or sterilization system according to one embodiment of the present disclosure.

Fig. 2 is a schematic view of an exemplary disinfection or sterilization system of another embodiment of the present disclosure.

In the drawings, like numbering represents like elements. While the above-identified drawing figures, which may not be drawn to scale, set forth various embodiments of the disclosure, other embodiments are also contemplated, as noted in the detailed description. In all cases, this disclosure describes the presently disclosed disclosure by way of representation of exemplary embodiments and not by express limitations. It should be understood that numerous other modifications and embodiments can be devised by those skilled in the art that will fall within the scope and spirit of the principles of this disclosure.

Detailed Description

Certain terms are used throughout the description and claims, and although mostly known, some explanation may be required. It is to be understood that, as used herein, the following terms have the meanings defined in the following glossary, unless a different definition is explicitly provided in the claims or elsewhere in this specification, including the drawings.

Glossary

The terms "sterilize" and "sterilization" and derivatives thereof are used to describe systems and methods for achieving a reduction in the amount of pathogenic agents, such as bacteria, viruses, spores and other microorganisms, on the surface of an article, such as a medical article (e.g., a medical instrument or endoscope lumen). It will be appreciated that sterilization is generally a sterilization that achieves a higher reduction in the amount of pathogens. Throughout the specification (including the claims), the term "disinfection" encompasses the term "sterilization".

The term "about" or "approximately" with respect to a numerical value or shape means +/-5% of the numerical value or attribute or characteristic, but expressly includes the exact numerical value. For example, a viscosity of "about" 1Pa-sec refers to a viscosity of 0.95 to 1.05Pa-sec, but also specifically includes a viscosity of exactly 1 Pa-sec.

As used in this specification and the appended embodiments, the singular forms "a", "an" and "the" include plural referents unless the content clearly dictates otherwise. Thus, for example, reference to a fine fiber comprising "a compound" includes mixtures of two or more compounds. As used in this specification and the appended embodiments, the term "or" is generally employed in its sense including "and/or" unless the content clearly dictates otherwise.

The term "substantially" particularly refers to an attribute or characteristic, meaning that the attribute or characteristic is more pronounced than it is. For example, a substrate that is "substantially" transparent refers to a substrate that transmits more radiation (e.g., visible light) than it does not. Thus, a substrate that transmits more than 50% of visible light incident on its surface is substantially transparent, but a substrate that transmits 50% or less of visible light incident on its surface is not substantially transparent.

As used in this specification, the recitation of numerical ranges by endpoints includes all numbers subsumed within that range (e.g. 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.8, 4, and 5).

Unless otherwise indicated, all numbers expressing quantities or ingredients, property measurements, and so forth used in the specification and embodiments are to be understood as being modified in all instances by the term "about". Accordingly, unless indicated to the contrary, the numerical parameters set forth in the foregoing specification and attached list of embodiments can vary depending upon the desired properties sought to be obtained by those skilled in the art utilizing the teachings of the present disclosure. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claimed embodiments, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

Various modifications and alterations may be made to the exemplary embodiments of the present disclosure without departing from the spirit and scope thereof. Therefore, it is to be understood that the embodiments of the present disclosure are not limited to the exemplary embodiments described below, but rather are controlled by the limitations set forth in the claims and any equivalents thereof.

Various exemplary embodiments of the present disclosure will now be described with particular reference to the accompanying drawings.

Exemplary Disinfection or Sterilization System

The present disclosure describes a sanitizing or sterilizing system comprising an enclosed chamber and a source of sanitizing vapor connected to the enclosed chamber, wherein the sanitizing vapor comprises nitric acid. The sterilization or disinfection system may be further described with respect to two different embodiments.

Embodiment 1: method for disinfecting or sterilizing nitric acid vaporized under atmospheric pressure

Turning to fig. 1, a schematic diagram of an exemplary sterilization system 2 of one embodiment of the present disclosure is shown. The sterilization system 2 includes an enclosed sterilization chamber 10 in fluid communication with a source of sterilization vapor 6 comprising nitric acid. An optional flow controller 13' (e.g., an electronic mass flow controller or flow control valve) may be used to regulate the flow of the sterilant vapor 6 into the sterilization chamber 10. An article (not shown in fig. 1) to be sterilized or disinfected may be placed with the disinfection chamber 10, such as through a sealable door, window, or port (not shown in fig. 1), and the chamber 10 may thereafter be sealed to effect sterilization or disinfection.

Optionally, the sterilization system 2 further comprises a gas source 4 in fluid communication with the closed sterilization chamber 10. An optional flow controller 13 (e.g., an electronic mass flow controller or flow control valve) may be used to regulate the flow of gas 4 into sterilization chamber 10. As shown in fig. 1, the flow of the gas source 4 may be combined with the flow of the sterilizing steam 6 into the sterilization chamber 10 after the flow controller 13 ', or alternatively may be combined with the sterilizing steam 6 before the flow controller 13' (not shown), or may even flow directly into the sterilization chamber 10 (not shown).

The gas source 4 may include molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof; air may advantageously be chosen. In certain exemplary embodiments, the sterilizing vapor 6 may include molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof. The gas source 4 may be air or a particular blend comprising molecular oxygen and molecular nitrogen in a particular ratio, and may be pressurized or unpressurized as provided. If from an unpressurized source, a compressor may be used to pressurize the gas to the appropriate pressure.

Optionally, the sterilization system 2 further comprises a source 8 of water vapor in a gas connected to the enclosure 10. An optional flow controller 13 "(e.g., an electronic mass flow controller or flow control valve) may be used to regulate the flow of the water vapor source 8 in the gas into the sterilization chamber 10. As shown in fig. 1, the flow of the water vapour source 8 in the gas may be combined with the flow of the sterilisation steam 4 into the sterilisation chamber 10 after the flow controller 13, or alternatively may be combined with the sterilisation steam 4 before the flow controller 13 (not shown), or may even flow directly into the sterilisation chamber 10 (not shown).

The gas may include molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof; air may advantageously be chosen. In some embodiments, the relative humidity of the water vapor source 8 in the gas may be at least 20%, 25%, 30%, 40%, 50%, 60%, or even at least 70%, and preferably less than 100%, 95%, 90%, 80%, or even 75%, depending on the temperature within the sterilization chamber 10.

In some embodiments, the temperature within sterilization chamber 10 may advantageously be maintained at a temperature that avoids condensation of liquid water within sterilization chamber 10. Typically, the temperature within the chamber is maintained at 20 ℃ to 100 ℃, 21 ℃ to 95 ℃, or even 22 ℃ to 90 ℃, although temperatures greater than 100 ℃ may be advantageously used. Generally, the temperature within the sterilization chamber 10 should be maintained below the temperature at which the contaminated articles will be damaged or degraded.

Various means for vaporizing or atomizing nitric acid in the sterilizing vapor, or for adding water vapor to the gas, such as a water-or nitric acid-containing gas bubbler, a bubbler, an atomizer, and a wick humidifier (not shown in fig. 1) may all be advantageously used. These means can be inserted from any position of the sterilization chamber 10 up to and including the source of sterilization steam 6, the source of gas 4 and/or the source of water steam 8.

The

optional flow controllers

13, 13' and 13 "may be independently selected as any means for adjusting the flow rate of the sterilizing steam 6. Suitable devices include pressure regulators, flow control valves, bulb flow meters (rotameters), electronic mass flow controllers, or other similar devices.

Optionally, the sterilization chamber 10 is connected to a device 12 for removing at least a portion of the nitric acid from the sterilization vapor 6. The means 12 for removing at least a portion of the nitric acid from the sterilizing vapor 6 may include a material selected from the group consisting of a basic functional compound, a reducing agent, a basic absorbent, a basic adsorbent, a catalyst, activated carbon, a molecular sieve, or combinations thereof.

In a convenient embodiment, the means 12 for removing at least a portion of the nitric acid from the sterilizing vapor 6 is a filter that includes a basic element such as sodium bicarbonate to neutralize any remaining acidic species. An optional filter element such as activated carbon may also be conveniently present to remove oxidizing substances such as ozone.

It is generally preferred that 100%, or alternatively at least 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, or even at least 90% of the nitric acid in the sterilizing vapor 6 is removed by the device 12 for removing at least a portion of the nitric acid from the sterilizing vapor 6. After the desired portion of nitric acid is removed from the sterilizing vapour 6, the remaining sterilizing vapour 6 may be released to ambient conditions.

Embodiment 2: vacuum pulse vaporization nitric acid disinfection or sterilization method

Turning to fig. 2, a schematic diagram of an exemplary decontamination system 22 of an alternative embodiment of the present disclosure is shown. The sterilization system 22 includes an enclosed sterilization chamber 30 in fluid communication with a sterilization vapor source 26 comprising nitric acid. An optional flow controller 23 may be used to regulate the flow of sterilant vapor 26 into the sterilization chamber 30. An article (not shown in fig. 2) to be sterilized or disinfected may be placed with the disinfection chamber 30, such as through a sealable door, window, or port (not shown in fig. 2), and the chamber 30 may thereafter be sealed to effect sterilization or disinfection.

The enclosed chamber 30 is connected to a vacuum pump 32 (e.g., a single or multi-stage rotary vacuum pump, a molecular jet pump, a diffusion pump, etc.) that may be isolated from the sterilization chamber 30 by an optional valve 36. A vacuum gauge 34 (e.g., a pressure gauge, a hot wire ionization gauge, a michael gauge, a penning gauge, a pirani gauge, etc.) may be connected to the enclosed chamber 30 to allow monitoring of the pressure within the chamber 30.

The sterilization system 22 includes a source 28 of water vapor in gas connected to a sterilization chamber 30. An optional flow controller 23' (e.g., an electronic mass flow controller or flow control valve) may be used to regulate the flow of the water vapor source 28 in the gas into the sterilization chamber 10. As shown in fig. 2, the flow of the water vapor source 28 in the gas may be combined with the flow of the sterilizing vapor 26 after the flow controller 23 into the sterilizing chamber 30, or alternatively, may be combined with the sterilizing vapor 26 before the flow controller 23 (not shown), or may even flow directly into the sterilizing chamber 30 (not shown).

The gas may include molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof; air may advantageously be chosen. In some embodiments, the relative humidity of the water vapor source 28 in the gas may be at least 20%, 25%, 30%, 40%, 50%, 60%, or even at least 70%, and preferably less than 100%, 95%, 90%, 80%, or even 75%, depending on the temperature within the sterilization chamber 30.

In some embodiments, the temperature within sterilization chamber 30 may advantageously be maintained at a temperature that avoids condensation of liquid water within sterilization chamber 30. Typically, the temperature within the chamber is maintained at 20 ℃ to 100 ℃, 21 ℃ to 95 ℃, or even 22 ℃ to 90 ℃, although temperatures greater than 100 ℃ may be advantageously used. Generally, the temperature within the sterilization chamber 10 should be maintained below the temperature at which the contaminated articles will be damaged or degraded.

Various means for vaporizing or atomizing nitric acid in the sterilizing vapor, or for adding water vapor to the gas, such as a water-or nitric acid-containing gas bubbler, a bubbler, an atomizer, and a wick humidifier (not shown in fig. 2) may all be advantageously used. These devices may be inserted from any location in the sterilization chamber 30 up to and including the source of sterilization steam 26, and/or the source of water steam 28.

Optional flow controllers 23 and 23' may be independently selected as any means for regulating the flow rate of the sterilizing vapor 26. Suitable devices include pressure regulators, flow control valves, bulb flow meters (rotameters), electronic mass flow controllers, or other similar devices.

Optionally, the sterilization chamber 30 is connected to a means (not shown) for removing at least a portion of the nitric acid from the sterilization vapor 26. The means for removing at least a portion of the nitric acid from the sterilizing vapor 26 may be positioned in fluid communication with the sterilization chamber 30, but is preferably placed in fluid communication between the sterilization chamber 30 and the vacuum pump 32, or on an exhaust from the vacuum pump.

The means for removing at least a portion of the nitric acid from the sanitizing vapor 26 can include a material selected from the group consisting of a basic-functional compound, a reducing agent, a basic absorbent, a basic adsorbent, a catalyst, activated carbon, a molecular sieve, or combinations thereof. In a convenient embodiment, the means 12 for removing at least a portion of the nitric acid from the sterilizing vapor 26 is a filter that includes a basic element, such as sodium bicarbonate, to neutralize any remaining acidic species. An optional filter element such as activated carbon may also be conveniently present to remove oxidizing substances such as ozone.

It is generally preferred that 100%, or alternatively at least 99%, 98%, 97%, 96%, 95%, 94%, 93%, 92%, 91%, or even at least 90% of the nitric acid in the sterilizing vapor 26 is removed by the apparatus for removing at least a portion of the nitric acid from the sterilizing vapor 26. After the desired portion of nitric acid is removed from the sterilizing vapor 26, the remaining sterilizing vapor 26 may be released to ambient conditions.

Method for generating sterilizing steam

In each of the disinfecting or sterilizing systems of embodiment 1 or embodiment 2 as described above, the disinfecting vapor comprising nitric acid is used to effect disinfection or sterilization of the soiled article.

As mentioned above, various means of forming a sterilizing vapour may advantageously be used to vaporise the nitric acid to form the sterilizing

vapour

6 or 26. In certain exemplary embodiments, nitric acid may be advantageously vaporized from an aqueous solution by flowing a gas stream through a gas bubbler or bubbler containing aqueous nitric acid, with or without heating the aqueous nitric acid. The nitric acid may be vaporized into a flowing gas stream using vacuum evaporation, atmospheric evaporation, flash evaporation, or atomization. Various vacuum evaporators, atmospheric evaporators, flash evaporators, atomizers and wick humidifiers may be used. These means for generating a sterilisation steam can be inserted from any position of the sterilisation chamber 30 up to and including the source of sterilisation steam 26, and/or the source of water steam 28.

Various methods may be used to prepare aqueous nitric acid, as described further below.

By oxidation of ammonia to form nitric acid (Ostwald process)

The method involves three stages: (1) ammonia oxidation, (2) nitric oxide oxidation, and (3) absorption of the resulting nitrogen oxides.

Stage 1：

Process conditions：

Catalyst: platinum (commonly used 90% Pt/10% Rd)

Pressure: 1-4 atmospheres (atm)

Temperature: about 1100 deg. K

Stage 2：

Process conditions：

Catalyst: is free of

Pressure: about 8atm

Temperature: about 300K

Stage 3：

Process conditions：

The reaction and distillation typically occur simultaneously in a staged distillation column.

Catalyst: is free of

Pressure: 11-14atm

Temperature: N/A

Formation of nitric acid by thermal decomposition of copper nitrate

The process involves two reactions carried out in a single stage.

The steam-forming reaction and distillation generally occur simultaneously in a stepwise manner.

A distillation column.

Process conditions：

Catalyst: is free of

Pressure: 11-14atm

Temperature: N/A

Preparation of nitric acid by reaction of sodium nitrate with sulfuric acid

The process involves a single stage and may be preferred.

Condition：

The nitric acid was boiled off and condensed into a collection vessel to separate from the sodium sulfate.

Soiled article

In each of the sterilization systems of embodiment 1 or embodiment 2 as described above, the contaminated article subjected to sterilization is inserted into the closed sterilization chamber (10 or 30) and sealed. The contaminated article may be a medical article, for example, a medical article selected from a medical dressing, a medical device, or a combination thereof. In certain embodiments, the medical device is an endoscope having a hollow lumen, and the sterilizing steam is passed through the hollow lumen of the endoscope to effect sterilization or disinfection.

The soiled article may be soiled with at least one of: a biofilm consisting of a plurality of microorganisms, a biofilm consisting of a plurality of microbial spores, a biofilm consisting of a plurality of fungal spores, or a plurality of fungal spores. The biofilm may comprise a plurality of microorganisms selected from the group consisting of: bacillus stearothermophilus (Geobacillus stearothermophilus), Bacillus subtilis (Bacillus subtilis), Bacillus atrophaeus (Bacillus atrophaeus), Bacillus megaterium (Bacillus megaterium), Bacillus coagulans (Bacillus coagulogenes), Clostridium producing (Clostridium sporogenes), Bacillus pumilus (Bacillus pumilus), Aspergillus brasiliensis (Aspergillus brasiliensis), Aspergillus oryzae (Aspergillus oryzae), Aspergillus niger (Aspergillus niger), Aspergillus nidulans (Aspergillus nidulans), Aspergillus flavus (Aspergillus flavus), Clostridium difficile (Clostridium difficile), Mycobacterium tuberculosis (Mycobacterium tuberculosis), Mycobacterium tuberculosis (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus epidermidis), Staphylococcus aureus (Staphylococcus aureus), Escherichia coli (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Bacillus subtilis), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis), Bacillus, Propionibacterium acnes (Propionibacterium acnes), Klebsiella pneumoniae (Klebsiella pneumoniae), Enterobacter cloacae (Enterobacter cloacae), Proteus mirabilis (Proteus mirabilis), Salmonella enterica (Salmonella enterica), Salmonella typhi (Salmonella typhi), Shigella (Shigella flexiriri), and combinations thereof.

Exemplary Disinfection or Sterilization Process

In another aspect, the present disclosure describes a method of disinfecting and/or sterilizing a soiled article. The method includes placing a contaminated product within an

enclosed sterilization chamber

10, 30 of a

sterilization system

2, 22, and treating the contaminated product within the enclosed

sterilization chamber

10, 30 with a source of

sterilization vapor

6, 26 comprising nitric acid for a treatment time sufficient to sterilize the contaminated product by achieving a reduction in the number of colony forming units of the sterilized contaminated product relative to the contaminated product. Optionally, the

closed sterilization chamber

10, 30 is connected to a vacuum pump 32.

In an exemplary embodiment, the sterilizing vapor further comprises a gas selected from molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof. The sterilizing vapor may include air.

In some embodiments, subjecting the soiled article within the enclosed chamber to the source of sanitizing steam may comprise alternately subjecting the soiled article to sanitizing steam for a first time interval and subjecting the soiled article to water steam for a second time interval. In some such embodiments, the subjecting of the soiled article to the sterilizing steam for a first time interval and the subjecting of the soiled article to the water steam for a second time interval is performed at least two times, at least three times, at least four times, at least five times, at least six times, at least seven times, at least eight times, at least nine times, or even at least 10 times, alternately. In certain such embodiments, the subjecting of the soiled article to the sterilizing steam for a first time interval and the subjecting of the soiled article to the water steam for a second time interval is carried out alternately up to 20 times, up to 10 times, up to 8 times, up to 7 times, up to 6 times, or even up to 5 times.

In certain exemplary embodiments, the method further comprises removing at least a portion of the vaporized nitric acid from the gas while achieving a desired degree of sterilization of the article. The removal of nitric acid from the disinfection vapor may advantageously be carried out using a material selected from the group consisting of basic functional compounds, reducing agents, basic absorbents, basic adsorbents, catalysts, activated carbon, molecular sieves, or combinations thereof.

In some embodiments, the removal of vaporized nitric acid from a gas may be performed with an apparatus 12 comprising one or more adsorbents or absorbent materials selected from the group consisting of activated carbon, chemicals having basic functional groups (e.g., organic amines, sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.), substances that provide basic adsorbents (e.g., basic ion exchange resins), reducing substances (e.g., one or more active metals, such as platinum, palladium, etc.), and molecular sieves. In some exemplary embodiments, removing vaporized nitric acid from a gas may be performed by directing the gas through a catalytic reducing agent.

In certain embodiments, the contaminated article is a medical article. The medical article may be selected from a medical dressing, a medical device, or a combination thereof. In certain presently preferred embodiments, the medical device is an endoscope having a hollow lumen, and the sterilizing steam is passed through the hollow lumen of the endoscope.

In some exemplary embodiments, the contaminated article is contaminated with at least one of: a biofilm comprising a plurality of microorganisms, a biofilm comprising a plurality of microbial spores, a biofilm comprising a plurality of fungal spores, or a plurality of fungal spores. In certain exemplary embodiments, the contaminated article is contaminated with a biofilm comprising a plurality of microorganisms selected from the group consisting of: bacillus stearothermophilus (Geobacillus stearothermophilus), Bacillus subtilis (Bacillus subtilis), Bacillus atrophaeus (Bacillus atrophaeus), Bacillus megaterium (Bacillus megaterium), Bacillus coagulans (Bacillus coagulogenes), Clostridium producing (Clostridium sporogenes), Bacillus pumilus (Bacillus pumilus), Aspergillus brasiliensis (Aspergillus brasiliensis), Aspergillus oryzae (Aspergillus oryzae), Aspergillus niger (Aspergillus niger), Aspergillus nidulans (Aspergillus nidulans), Aspergillus flavus (Aspergillus flavus), Clostridium difficile (Clostridium difficile), Mycobacterium tuberculosis (Mycobacterium tuberculosis), Mycobacterium tuberculosis (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus epidermidis), Staphylococcus aureus (Staphylococcus aureus), Escherichia coli (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Bacillus subtilis), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis), Bacillus, Propionibacterium acnes (Propionibacterium acnes), Klebsiella pneumoniae (Klebsiella pneumoniae), Enterobacter cloacae (Enterobacter cloacae), Proteus mirabilis (Proteus mirabilis), Salmonella enterica (Salmonella enterica), Salmonella typhi (Salmonella typhi), Shigella (Shigella flexiriri), and combinations thereof.

In any of the preceding embodiments, the treatment time is at least 1 minute and at most 10 minutes. Preferably, the treatment time to achieve the desired level of disinfection is selected to be at most 9 minutes, 8 minutes, 7 minutes, 6 minutes, 5 minutes, or even at most 4 minutes, 3 minutes, 2 minutes, or even 1 minute.

In any of the preceding embodiments, the sterilized article has at least a 2-log reduction in colony forming units relative to the contaminated article₁₀And at most 11-log₁₀Reduction of (a) of at least 3-log₁₀And at most 11-log₁₀Reduction of (a) of at least 4-log₁₀And at most 11-log₁₀Reduction of (a) of at least 5-log₁₀And at most 11-log₁₀Reduction of (a) of at least 6-log₁₀And at most 11-log₁₀Reduction of (a) of at least 7-log₁₀And at most 11-log₁₀Reduction of (a) of at least 8-log₁₀And at most 11-log₁₀Reduction of (a) of at least 9-log₁₀And at most 11-log₁₀Or even at least 10-log₁₀And at most 11-log₁₀Is reduced.

The operation of the exemplary embodiments of the present disclosure will be further described with reference to the non-limiting specific examples detailed below. These examples are provided to further illustrate various specific and preferred embodiments and techniques. It should be understood, however, that many variations and modifications may be made while remaining within the scope of the present disclosure.

Examples

These examples are for illustrative purposes only and are not intended to unduly limit the scope of the appended claims. Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the disclosure are approximations, the numerical values set forth in the specific examples are reported as precisely as possible. Any numerical value, however, inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of the claims, each numerical parameter should at least be construed in light of the number of reported significant digits and by applying ordinary rounding techniques.

Material

All parts, percentages, ratios, and the like in the examples and the remainder of the specification are by weight unless otherwise indicated. Solvents and other reagents used were, unless otherwise indicated, available from Sigma Aldrich Chemical Company of Milwaukee, WI. In addition, table 1 provides abbreviations and sources for all materials used in the following examples:

table 1: material

Preparation of spore samples

A sample of PET film was cut ((1 × 2cm) and placed in a petri dish, then, 10. mu.L of Geobacillus stearothermophilus spores (about 1 × 10)⁸CFU/mL, vortex for 1 minute) drop cast onto each membrane the membranes contained about 1 × 10⁶Spores/membranes. The membrane was allowed to dry under ambient conditions with the lid of the petri dish open for at least 1 hour to ensure complete drying of the sample.

For some experiments, the membranes were inserted into PTFE sample tubing using clean forceps, with 3 membranes inserted per sample tube. The membranes were checked to ensure there was no significant overlap in spore spots and the membranes were in PTFE tubes with the spores facing the inside of the tube. For other experiments, the films were inserted into Steri-Lok8502 bags prior to treatment.

Spore sample collection and colony enumeration

A solution of 1X phosphate buffered saline (1XPBST) was prepared from 100mL phosphate buffered saline 10X concentrate, 900mL deionized water, and 1g Tween 80 surfactant. The 1XPBST solution was mixed on a stir plate for 5 minutes and then vacuum filtered through a 0.2 μm vacuum filter to ensure sterility and stored at 4 ℃. After the sterilization treatment, the spore coat was removed using sterile forceps. The membrane was then immediately transferred to a 50mL tube containing 25mL of 1XPBST to neutralize the pH and any oxidizing species. The 50mL tubes were immediately vortexed, then sonicated for 20 minutes, and vortexed again to ensure that all spores were removed from the surface.

One ml sample of the buffer solution containing spores was diluted in Butterfield buffer. A series of dilutions with 10-fold, 100-fold and 1000-fold reductions in concentration were performed, since the original sample contained 10-fold⁶Individual colonies, it was necessary to reduce the concentration to be counted. One milliliter of the appropriate dilution series made from the treated membrane sample and the untreated (control) sample in 1XPBST was then spread onto

The above. Will be provided with

The plates were placed on an aluminum pan and the spores were placed in an oven at an optimal growth temperature of 56 ℃ so that colonies could grow in the presence of Colony Forming Units (CFU).

After incubation of the spores, the number of colony forming units was counted. Control samples of in each case untreated spore membranes were used as standards. For ideal quantification of kill, each

The number of CFUs (g) of (a) is quantified in the range of 20-200. Based on the number of CFUs and the known dilution concentration, the number of original CFUs can be calculated from the control or treated spore coat, and the amount of spore kill quantified.

Apparatus and method

The sterilization apparatus used in these examples is schematically shown in fig. 2 and comprises an enclosed sterilization chamber 30, a vacuum pump 32, a vacuum gauge 34 and solenoid valves 23 and 23' connecting nitric acid and a water source. The sterilization chamber 30 has a volume of 10L.

Example 1

In a separate container, 10mL of 68.8% nitric acid and 10mL of water are added. The killing efficacy was tested by first preparing a sample of Geobacillus stearothermophilus according to the test method above. Three inoculated PET strips were placed in a 3M Steri-Lok8502 bag. The bags were then heat sealed and placed in the chamber of a sterilization apparatus. The chamber was evacuated to a pressure drop to a baseline pressure of 0.5 torr. The roughing pump valve is then closed, isolating the vacuum chamber. The valves for the nitric acid solution were then opened for the times specified in table 2. Subsequently, the valve to the nitric acid delivery system was closed and the valve to the water source was opened for the time specified in table 2. The valve to the water supply is then closed and the valve to the pump is opened, returning the chamber to the base pressure.

Table 2: kill efficacy as a function of treatment time and cycle number.

The process is repeated for the indicated number of cycles. After the cycle is completed, the valves of the pump are closed and humid air is used to vent the system up to 700 torr. The chamber was then evacuated to the baseline pressure. This process was repeated three times and the chamber was then allowed to equilibrate at atmospheric pressure. After treatment, the chamber was vented, the sample film was collected, and spores were counted as described above. The first row of results in table 2 represents control conditions. The control sample had a 6.1Log₁₀Average of CFU/sample. Subsequent samples were counted without dilution. Samples with no growth showed a negative result and samples with the number of colony forming units showed a positive result.

Example 2

Sterilization efficacy of intraluminal

The killing efficacy of the interior of the narrow lumen was tested by first preparing a sample of Geobacillus stearothermophilus according to the test method described above. Three inoculated PET strips were placed in the middle of a 6 foot length of PTFE tubing with an 1/8 "diameter lumen. The tube was then placed in the vacuum chamber described in example 1. Using the method described in example 1, 2 cycles were passed through HNO₃And H₂O treatment for 60 seconds. After treatment, the chamber was vented, the sample film was collected, and spores were counted as described above. All treated samples showed no growth after 48 hours.

Example 3:

atmospheric evaporation of nitric acid

Sterilization apparatus was constructed using a 25mm OD × 200mm Sigma-Aldrich vacuum trap as the bubbling unit, HNO was prepared at 45% wt% HNO3₃At H₂Aqueous solution in O. 5.4mL of the solution was injected into the bottom of the bubbling unit. A mixture of 500 standard cubic centimeters per minute (SCCM) oxygen and 1750SCCM nitrogen was bubbled through the bubbling unit. The output from the sparging unit was sent through PTFE tubing to a tee where it was mixed with additional 750SCCM nitrogen. The total mixture was conveyed from the tee through a 1/8"ID PTFE tubing. The spore coated membrane was inserted into the PTFE tubing 6 feet (about 1.83m) downstream of the steam mixing device. The membranes were treated with the gaseous mixture for a total of 5 minutes. Initial spore concentration of 6.2Log was measured₁₀CFU/sample. In vaporized HNO₃After treatment of the mixture, no colony forming units were observed.

Comparative example 1

₃Liquid HNO

Preparation of HNO with 5 wt% HNO3₃And H₂A liquid solution of O. Geobacillus stearothermophilus coated membranes were prepared. Thirty microliters of HNO₃The solution was drop cast onto the spores, covering the area of inoculation. The solution was allowed to stand on the membrane for 5 minutes, and then the membrane was buffered in 25mL of 1 XPBST. Subsequent reclamation is accomplished as previously described. After passing through HNO₃Prior to processing, 5.9Log was recovered₁₀CFU/sample. After passing through HNO₃After 5 minutes of solution treatment, 5.4Log was recovered₁₀CFU/sample.

Reference throughout this specification to "one embodiment," "certain embodiments," "one or more embodiments," or "an embodiment," whether or not including the term "exemplary" preceding the term "embodiment," means that a particular feature, structure, material, or characteristic described in connection with the embodiment is included in at least one embodiment of the certain exemplary embodiments of the present disclosure. Thus, the appearances of the phrases such as "in one or more embodiments," "in certain embodiments," "in one embodiment," or "in an embodiment" in various places throughout this specification are not necessarily referring to the same embodiment of the certain exemplary embodiments of the present invention. Furthermore, the particular features, structures, materials, or characteristics may be combined in any suitable manner in one or more embodiments.

Moreover, all publications and patents cited herein are incorporated by reference in their entirety to the same extent as if each individual publication or patent were specifically and individually indicated to be incorporated by reference. Various exemplary embodiments have been described.

While this specification has described in detail certain exemplary embodiments, it will be appreciated that those skilled in the art, upon attaining an understanding of the foregoing, may readily conceive of alterations to, variations of, and equivalents to these embodiments. Accordingly, it should be understood that the present disclosure should not be unduly limited to the illustrative embodiments set forth hereinabove. These and other embodiments are within the scope of the following claims.

Claims

1. A sterilization system, the sterilization system comprising:

a closed chamber; and

a source of sanitizing vapor connected to the enclosed chamber, wherein the sanitizing vapor comprises nitric acid, optionally wherein the enclosed chamber is connected to a vacuum pump.

2. The sterilizing system of claim 1 wherein the sterilizing vapor further comprises a gas selected from molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof.

3. The sterilizing system of claim 2 wherein the sterilizing vapor comprises air.

4. The sterilization system according to claim 1, further comprising a source of water vapor in a gas connected to the closed chamber, wherein the gas is selected from molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof, optionally wherein the relative humidity of the water vapor in the gas is at least 20%.

5. The sterilization system of claim 1, further comprising means for removing at least a portion of the nitric acid from the sterilization vapor, optionally wherein the means comprises a material selected from the group consisting of: a basic functional compound, a reducing agent, a basic absorbent, a basic adsorbent, a catalyst, activated carbon, a molecular sieve, or a combination thereof.

6. The sterilization system of claim 1, further comprising a contaminated article undergoing sterilization, optionally wherein the contaminated article is contaminated with at least one of: a biofilm consisting of a plurality of microorganisms, a biofilm consisting of a plurality of microbial spores, a biofilm consisting of a plurality of fungal spores, or a plurality of fungal spores.

7. The sterilization system of claim 6, wherein the contaminated article is a medical article, optionally wherein the medical article is selected from a medical dressing, a medical device, or a combination thereof.

8. The sterilization system according to claim 7, wherein the medical device is an endoscope comprised of a hollow lumen, further wherein the sterilization vapor passes through the hollow lumen of the endoscope.

9. The sterilization system according to claim 6, wherein the biofilm is comprised of a plurality of microorganisms selected from the group consisting of: bacillus stearothermophilus (Geobacillus stearothermophilus), Bacillus subtilis (Bacillus subtilis), Bacillus atrophaeus (Bacillus atrophaeus), Bacillus megaterium (Bacillus megaterium), Bacillus coagulans (Bacillus coagulogenes), Clostridium producing (Clostridium sporogenes), Bacillus pumilus (Bacillus pumilus), Aspergillus brasiliensis (Aspergillus brasiliensis), Aspergillus oryzae (Aspergillus oryzae) Aspergillus oryzae (Aspergillus oryzae), Aspergillus niger (Aspergillus niger), Aspergillus nidulans (Aspergillus nidulans), Aspergillus flavus (Bacillus difficile), Clostridium difficile (Clostridium difficile), Mycobacterium tuberculosis (Mycobacterium tuberculosis), Mycobacterium tuberculosis (Staphylococcus aureus), Escherichia coli (Staphylococcus epidermidis), Staphylococcus aureus (Staphylococcus aureus), Escherichia coli (Staphylococcus aureus), Staphylococcus aureus (Bacillus subtilis), Bacillus subtilis (Bacillus subtilis), Bacillus subtilis (Staphylococcus aureus), Bacillus subtilis (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus aureus), Staphylococcus aureus (Staphylococcus aureus), Bacillus subtilis), and Bacillus subtilis), Bacillus, Propionibacterium acnes (Propionibacterium acnes), Klebsiella pneumoniae (Klebsiella pneumoniae), Enterobacter cloacae (Enterobactercloacae), Proteus mirabilis (Proteus mirabilis), Salmonella enterica (Salmonella enterica), Salmonella typhi (Salmonella typhi), Shigella flexiriri (Shigella flexirii), and combinations thereof.

10. A method of disinfecting a soiled article, said method comprising:

placing the contaminated article within an enclosed chamber of a sterilization system, optionally wherein the enclosed chamber is connected to a vacuum pump; and

treating the contaminated article within the enclosed chamber with a source of sterilizing steam comprising nitric acid for a treatment time sufficient to sterilize the contaminated article by achieving a reduction in the number of colony forming units of the sterilized contaminated article relative to the contaminated article, optionally wherein the treatment time is at most ten minutes.

11. The method of claim 10, wherein the sterilizing vapor further comprises a gas selected from molecular oxygen, molecular nitrogen, helium, neon, argon, krypton, or combinations thereof.

12. The method of claim 11, wherein the sterilizing vapor comprises air.

13. The method of claim 11, wherein subjecting the contaminated article within the enclosed chamber to the source of sanitizing steam comprises alternately subjecting the contaminated article to the sanitizing steam for a first time interval and subjecting the contaminated article to water steam for a second time interval, optionally wherein alternately subjecting the contaminated article to the sanitizing steam for the first time interval and subjecting the contaminated article to the water steam for the second time interval is performed at least twice.

14. The method of claim 10, further comprising removing the nitric acid from the sterilizing vapor using a material selected from the group consisting of: a basic functional compound, a reducing agent, a basic absorbent, a basic adsorbent, a catalyst, activated carbon, a molecular sieve, or a combination thereof.

15. The method of claim 10, wherein the contaminated article is contaminated with at least one of: a biofilm consisting of a plurality of microorganisms, a biofilm consisting of a plurality of microbial spores, a biofilm consisting of a plurality of fungal spores, or a plurality of fungal spores.

16. The method of claim 15, wherein the contaminated article is a medical article, optionally wherein the medical article is selected from a medical dressing, a medical device, or a combination thereof.

17. The method of claim 16, wherein the medical device is an endoscope comprised of a hollow lumen, further wherein the sterilizing vapor is passed through the hollow lumen of the endoscope.

18. The method of claim 15, wherein the contaminated article is contaminated with a biofilm comprising a plurality of microorganisms selected from the group consisting of: geobacillus stearothermophilus, Bacillus subtilis, Bacillus atrophaeus, Bacillus megaterium, Bacillus coagulans, Clostridium sporogenes, Bacillus pumilus, Aspergillus brazilian, Aspergillus oryzae, Aspergillus niger, Aspergillus nidulans, Aspergillus flavus, Clostridium difficile, Mycobacterium geotrichum, Mycobacterium tuberculosis, Mycobacterium bovis, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus epidermidis, Staphylococcus lucentis, Staphylococcus saprophyticus, enterococcus faecium, enterococcus faecalis, Propionibacterium acnes, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Salmonella enterica, Salmonella typhi, Shigella, and combinations thereof, further wherein the treatment time is at least 1 minute, and the sterilized article has at least a 2-log reduction in colony forming units relative to the contaminated article.₁₀And at most 11-log₁₀Optionally wherein the treatment time is at most six minutes.

19. The method of claim 15, wherein the contaminated article is contaminated with a plurality of microorganisms, further wherein the treatment time is at least 1 minute and the reduction in colony forming units of the sterilized article relative to the contaminated article is at least 4-log₁₀And at most 9-log₁₀Optionally wherein the treatment time is up to six minutes.

20. The method of any one of claims 21 to 24, wherein the contaminated article is contaminated with a plurality of microbial spores or a plurality of fungal spores, wherein the treatment time is at least 1 minute and the reduction in the number of colony forming units of the sterilized article relative to the contaminated article is at least 6-log₁₀And at most 10-log₁₀Optionally wherein the treatment isThe time period is up to six minutes.